Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
24388013
TITLE
Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever.
OBJECTIVE NlmCategory: OBJECTIVE
We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases.
METHODS NlmCategory: METHODS
We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091).
RESULTS NlmCategory: RESULTS
At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10(-8)). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10(-6)).
CONCLUSION NlmCategory: CONCLUSIONS
By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.
Copyright 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
DATE PUBLISHED
2014 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/05/31
revised 2013/10/03
accepted 2013/10/09
aheadofprint 2013/12/31
entrez 2014/01/07 06:00
pubmed 2014/01/07 06:00
medline 2014/07/19 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Ferreira MA Ferreira Manuel A R MA QIMR Berghofer Medical Research Institute, Brisbane, Australia. Electronic address: manuel.ferreira@qimrberghofer.edu.au.
Matheson MC Matheson Melanie C MC Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Tang CS Tang Clara S CS QIMR Berghofer Medical Research Institute, Brisbane, Australia; Departments of Psychiatry, Surgery, and Medicine, Centre for Genomic Sciences, University of Hong Kong, Hong Kong, China.
Granell R Granell Raquel R School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
Ang W Ang Wei W School of Women's and Infant's Health, University of Western Australia, Subiaco, Australia.
Hui J Hui Jennie J PathWest Laboratory Medicine of Western Australia, Nedlands, Australia; School of Population Health, University of Western Australia, Nedlands, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, Australia; Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia.
Kiefer AK Kiefer Amy K AK 23andMe, Mountain View, Calif.
Duffy DL Duffy David L DL QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Baltic S Baltic Svetlana S Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia.
Danoy P Danoy Patrick P University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
Bui M Bui Minh M Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Price L Price Loren L Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia.
Sly PD Sly Peter D PD Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, Australia.
Eriksson N Eriksson Nicholas N 23andMe, Mountain View, Calif.
Madden PA Madden Pamela A PA Department of Psychiatry, Washington University School, of Medicine, St Louis, Mo.
Abramson MJ Abramson Michael J MJ Department of Epidemiology & Preventive Medicine, Monash University, Melbourne, Australia.
Holt PG Holt Patrick G PG Telethon Institute of Child Health Research, University of Western Australia, Subiaco, Australia.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School, of Medicine, St Louis, Mo.
Hunter M Hunter Michael M School of Population Health, University of Western Australia, Nedlands, Australia; Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia.
Musk B Musk Bill B School of Population Health, University of Western Australia, Nedlands, Australia; Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia; Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
Robertson CF Robertson Colin F CF Respiratory Medicine, Murdoch Children's Research Institute, Melbourne, Australia.
Le Souëf P Le Souëf Peter P School of Paediatrics and Child Health, Princess Margaret Hospital for Children, Perth, Australia.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Henderson AJ Henderson A John AJ School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
Tung JY Tung Joyce Y JY 23andMe, Mountain View, Calif.
Dharmage SC Dharmage Shyamali C SC Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
Brown MA Brown Matthew A MA University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
James A James Alan A Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia; Department of Pulmonary Physiology, West Australian Sleep Disorders Research Institute, Nedlands, Australia.
Thompson PJ Thompson Philip J PJ Lung Institute of Western Australia and Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Perth, Australia.
Pennell C Pennell Craig C School of Women's and Infant's Health, University of Western Australia, Subiaco, Australia.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Evans DM Evans David M DM School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, United Kingdom.
Hinds DA Hinds David A DA 23andMe, Mountain View, Calif.
Hopper JL Hopper John L JL Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia. Electronic address: j.hopper@unimelb.edu.au.
Australian Asthma Genetics Consortium Collaborators
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Nyholta Dale R DR
Beilbyb-d John J
Cheahe Faang F
Mészárosf Desiree D
Gordona Scott D SD
Southeyg Melissa C MC
Wrighta Margaret J MJ
Markosh James J
Chunge Li P LP
Hendersa Anjali K AK
Gilesi Graham G
Templee Suzanna S
Whitfielda John J
Sheltone Brad B
Mitrpante Chalermchai C
Jenkinsj Mark M
Waltersf Haydn H
JOURNAL
VOLUME: 133
ISSUE: 6
TITLE: The Journal of allergy and clinical immunology
ISOABBREVIATION: J. Allergy Clin. Immunol.
YEAR: 2014
MONTH: Jun
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1097-6825
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: J Allergy Clin Immunol
COUNTRY: United States
ISSNLINKING: 0091-6749
NLMUNIQUEID: 1275002
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites J Immunol. 2000 Jul 1;165(1):286-91 10861063
Cites PLoS One. 2012;7(9):e44008 23028483
Cites Biometrics. 1999 Dec;55(4):997-1004 11315092
Cites J Biol Chem. 2002 Mar 15;277(11):8890-7 11751910
Cites J Allergy Clin Immunol. 2002 Mar;109(3):419-25 11897985
Cites J Allergy Clin Immunol. 2003 Jun;111(6):1171-83; quiz 1184 12789212
Cites Nat Genet. 2004 Apr;36(4):388-93 15052270
Cites Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1351-8 2252253
Cites Lancet. 1993 Oct 9;342(8876):887-91 8105165
Cites Science. 1994 Jul 29;265(5172):682-4 8036519
Cites Early Hum Dev. 1996 Jul 19;45(3):203-14 8855394
Cites BMJ. 1997 Jun 28;314(7098):1864-8 9224128
Cites J Biol Chem. 1998 May 22;273(21):13097-103 9582348
Cites J Biol Chem. 1999 Mar 19;274(12):8123-8 10075714
Cites J Allergy Clin Immunol. 1999 Aug;104(2 Pt 1):301-4 10452748
Cites Clin Exp Allergy. 2006 Nov;36(11):1382-90 17083348
Cites Med J Aust. 2006 Nov 20;185(10):565-71 17115970
Cites Nat Genet. 2007 Jul;39(7):857-64 17554260
Cites Nature. 2007 Jul 26;448(7152):470-3 17611496
Cites N Engl J Med. 2007 Aug 30;357(9):851-62 17660530
Cites Nat Genet. 2007 Oct;39(10):1202-7 17873877
Cites J Allergy Clin Immunol. 2007 Oct;120(4):863-9 17825896
Cites Genet Epidemiol. 2008 May;32(4):381-5 18348202
Cites J Biol Chem. 2008 May 30;283(22):15134-41 18378679
Cites PLoS Biol. 2008 May 6;6(5):e107 18462017
Cites Lancet. 2008 Sep 20;372(9643):1049-57 18805333
Cites Am J Hum Genet. 2009 May;84(5):581-93 19426955
Cites Am J Hum Genet. 2009 Nov;85(5):745-9 19853236
Cites Nat Genet. 2010 Jan;42(1):36-44 20010834
Cites Nat Genet. 2010 Dec;42(12):1118-25 21102463
Cites Am J Hum Genet. 2010 Dec 10;87(6):779-89 21129726
Cites PLoS One. 2011;6(5):e19719 21625490
Cites Eur J Hum Genet. 2011 Jul;19(7):807-12 21407268
Cites PLoS Genet. 2011 Jul;7(7):e1002170 21814517
Cites Nat Genet. 2012 Nov;44(11):1222-6 23042114
Cites J Allergy Clin Immunol. 2012 Nov;130(5):1117-1122.e1 23021888
Cites Nature. 2012 Nov 1;491(7422):119-24 23128233
Cites Clin Exp Allergy. 2012 Dec;42(12):1724-33 23181788
Cites Genes Immun. 2013 Jan;14(1):62-6 23151489
Cites N Engl J Med. 2010 Jan 7;362(1):36-44 20032318
Cites Am J Hum Genet. 2010 Jan;86(1):88-92 20045101
Cites N Engl J Med. 2010 May 6;362(18):1686-97 20410501
Cites Nat Genet. 2010 Jun;42(6):508-14 20453842
Cites PLoS One. 2010;5(5):e10693 20502693
Cites Nature. 2010 Jul 1;466(7302):113-7 20596022
Cites Bioinformatics. 2010 Sep 1;26(17):2190-1 20616382
Cites N Engl J Med. 2010 Sep 23;363(13):1211-21 20860503
Cites Nat Genet. 2011 Apr;43(4):329-32 21399635
Cites Int J Epidemiol. 2013 Feb;42(1):111-27 22507743
Cites Nat Genet. 2013 Aug;45(8):907-11 23817569
Cites Nat Genet. 2013 Aug;45(8):902-6 23817571
Cites PLoS Genet. 2011 Aug;7(8):e1002216 21829393
Cites Nature. 2011 Aug 11;476(7359):214-9 21833088
Cites Nat Genet. 2011 Sep;43(9):893-6 21804548
Cites Nat Genet. 2011 Sep;43(9):887-92 21804549
Cites Lancet. 2011 Sep 10;378(9795):1006-14 21907864
Cites J Allergy Clin Immunol. 2011 Nov;128(5):996-1005 22036096
Cites Hum Mol Genet. 2012 Jan 15;21(2):322-33 21989056
Cites Nat Genet. 2012 Feb;44(2):187-92 22197932
Cites Hum Genet. 2012 May;131(5):747-56 22143225
Cites Nat Genet. 2012 May;44(5):502-10 22446964
Cites Clin Exp Allergy. 2012 Jul;42(7):1097-103 22702508
Cites Thorax. 2012 Sep;67(9):762-8 22561531
Cites Genet Epidemiol. 2001 Jan;20(1):4-16 11119293
GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
AA17688 NIAAA NIH HHS United States
DA12854 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
MC_PC_15018 Medical Research Council United Kingdom
MH66206 NIMH NIH HHS United States
MOP-82893 Canadian Institutes of Health Research Canada
P60 AA011998 NIAAA NIH HHS United States
R01 AA007535 NIAAA NIH HHS United States
R01 AA007728 NIAAA NIH HHS United States
R01 AA010249 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
Rhinitis
atopy
bivariate
genetic correlation
selection
single nucleotide polymorphism
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Alleles
Asthma genetics
Female genetics
Gene Frequency genetics
Genetic Variation genetics
Genome-Wide Association Study genetics
Humans genetics
Lectins, C-Type genetics
Linkage Disequilibrium genetics
Male genetics
Middle Aged genetics
Monosaccharide Transport Proteins genetics
Odds Ratio genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait Loci genetics
Repressor Proteins genetics
Rhinitis, Allergic, Seasonal genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CLEC16A protein, human
0 Lectins, C-Type
0 Monosaccharide Transport Proteins
0 Repressor Proteins
0 ZBTB10 protein, human
OTHER ID's
OTHERID SOURCE
NIHMS553108 NLM
PMC4280183 NLM